Our objeciive is to develop chemotherapeutic tools for the treatment of oral herpes simplex. In particular, we propose synthesizing new analogs of the naturally-occurring nucleoside arabinosylthymine (araT). These analogs will contain two independent inhibitory groups, the arabinosyl moeity as the sugar, and ethyl and methoxymethyl groups instead of the 5-methyl group of araT. We will evaluate the antiviral properties of these in cell culture and in vivo against herpes simplex virus (HSV) and equine herpes virus. We will also determine the ability of the analogs to inhibit cell growth, as well as mitogen stimulation of lymphoblast transformation. Further, we will assay their teratogenic potential in hamsters. We will explore their mechanism of action by comparing the newly-synthesized compounds with araT with respect to their ability 1) to serve as substrate for 1) the herpesviral-specified pyrimidine deoxyribonucleoside kinase (dPyK) and b) host thymidine kinase(s); and 2) inhibit DNA synthesis in herpesvirus-infected cells. While our findings may be applicable to a variety of herpesviruses, we beleive that because of the broader specificity of the dPyK of the herpes simplex virus type 1 (the predominant oro-facial type), araT and araT-like drugs will be more effective in dental therapy of oral lesions.